[4+3]-Cycloaddition/Quasi-Favorskii Processes

本项目致力于探索[4，3]-环加成/准Favorskii反应过程。这一反应序列提供了快速获得高度复杂结构的途径，将用于合成三种天然产物：前列腺素三环克拉维酮、生物碱麦哲罗酮和抗结核药物elisapterosin B。每一种天然产物都将允许一种独特的环烯丙基阳离子[4 3]-环加成反应的发展，从环戊烯基到环庚烯基。将研究两种不同的产生烯丙基阳离子的方案。环加合物的准Favorskii重排将是整个合成努力的组成部分。该反应将得到原则上可通过二烯与环烯基甲基醛的Diels-Alder环加成直接得到的化合物。不同环加成反应的立体化学差异表明，[4，3]-环加成反应更适合于目标的全合成。互补环加成过程将在与环戊二烯和其他环二烯的环加成过程中进行计算和实验比较。还将探索非环二烯的分子间和分子内[4，3]-环加成/准Favorskii过程。有了这个奖项，有机和高分子化学计划支持密苏里大学哥伦比亚分校化学系的Michael Harmata教授的研究。哈马塔教授和他的学生正在开发一种不同寻常的高效路线，用于快速构建复杂的有机分子结构。正在探索的方法学，将环加成反应与随后的分子重排反应相结合，将应用于几个自然产生的分子的合成，以建立其通用性和通用性。一般的想法是利用独特的工艺和简单的起始材料相结合来快速增加分子的复杂性。复杂的有机结构往往在新药或新材料的开发中发挥关键作用，随着分子医学和纳米技术的技术发展，新药物或新材料将变得越来越重要。

This project is focused on the exploration of a [4+3]-cycloaddition/quasi-Favorskii process. This reaction sequence, which provides rapid access to highly complex structures, will be applied to the synthesis of three natural products: the prostanoid tricycloclavulone, the alkaloid magellaninone and the antitubercular agent elisapterosin B. Each natural product will allow the development of the [4+3]-cycloaddition of a unique cyclic allylic cation, from cyclopentenyl to cycloheptenyl. Two different protocols for generating the allylic cations will be studied. The quasi-Favorskii rearrangement of the cycloadducts will be an integral part of the total synthesis efforts. This reaction will afford compounds that could in principle be obtained directly through the Diels-Alder cycloaddition of dienes with cycloalkenyl carboxaldehydes. Stereochemical differences between the cycloaddition processes suggest that the [4+3]-cycloaddition will be more suited for the total syntheses of the targets. The complementary cycloaddition processes will be compared both computationally and experimentally in the context of cycloadditions with cyclopentadiene and other cyclic dienes. Intermolecular and intramolecular [4+3]-cycloaddition/quasi-Favorskii processes of noncyclic dienes will also be explored.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Michael Harmata, of the Department of Chemistry at the University of Missouri at Columbia. Professor Harmata and his students are developing an unusual and efficient route for the rapid construction of complex organic molecular structures. The methodology under exploration, combining a ring-forming "cycloaddition" reaction with a subsequent molecular rearrangement reaction, will be applied to the synthesis of several naturally occurring molecules in order to establish its versatility and generality. The general idea is to take advantage of unique processes combined with simple starting materials to increase molecular complexity quickly. Complex organic structures often play critical roles in the development of new drugs or new materials that will be increasingly important as technological developments in molecular medicine and nanotechnology increase.